Drug resistance mechanism in TB found

Researchers at the Johns Hopkins Bloomberg School of Public Health and Huashan Hospital, Fudan University announced on Wednesday that their study has identified a new mechanism for Pyrazinamide resistance.

Tuberculosis is a common infectious disease cause by various strains of mycobacteria and is one of the world's leading causes of death, with almost 9 million cases of TB reported worldwide in 2010.

Tuberculosis attacks the lungs, and is sometimes known for attacking other parts of the body. It is spread by coughing and sneezing from people infected with TB.

Pyrazinamide is a drug used to combat TB by killing dormant persister bacteria, which is crucial in shortening TB therapy. The way the drug works has been somewhat of a mystery to scientists, and this made identifying why TB was becoming resistance to it that much more challenging.

"There is significant recent interest in understanding PZA, since it is the only TB drug that cannot be replaced without compromising the efficacy of the therapy," Ying Zhang, senior author of the study and professor in the Bloomberg School's W. Harry Feinstone Department of Molecular Microbiology and Immunology, said. "It's indispensible. The process of identifying the correct resistance mutations was quite tedious and took about two years to complete. However, the work led to the identification of a potential new mechanism of PZA resistance."

Earlier studies showed mutations in the pncA gene and the rpsA gene as the reasons for PZA resistance. The recent study shows that resistance to PZA is mainly caused by mutations in the pncA gene encoding enzyme nicotinamidase/pyrazinamidase.

The results also showrf that some TB bacteria lack the mutations in both these genes. The researchers found that a mutation in the panD gene may be to blame for some of the TB's bacteria resistance to PZA.